Blood Clotting

Question 1

Which coagulation test needs to be looked at for a patient on heparin?

Answer 1

Partial Thromboplastin Time (PTT), which measures the intrinsic pathway.

Question 2

What is thrombocytopenia?

Answer 2

Too few platelets.

Question 3

Which coagulation test needs to be looked at for a patient on warfarin?

Answer 3

Prothrombin Time (PT) which looks at the extrinsic pathway, and is used in the INR measurement.

Question 4

Name two clotting factors that circulate in the blood.

Answer 4

Factor VII, and factor X.

Question 5

What is thrombocytopenia?

Answer 5

Low circulating platelets.

Question 6

What is Glanzmann’s thrombasthenia?

Answer 6

An autosomal recessive condition which affects megakaryocytes and results in a lack of platelet aggregation. It can be deected using platelet aggregometry.

Question 7

What is haemophilia A?

Answer 7

Deficiency in factor 8.

Question 8

What is haemophilia B?

Answer 8

Deficiency in factor 9.

Question 9

How is the intrinsic pathway of coagulation initiated?

Answer 9

There is damage to the wall of the blood vessel (can be atherosclerosis caused by scavenger macrophages absorbing too much LDL) which causes factor XII in the blood to be activated.
This activates factor XI, which activates factor IX, which forms a complex with factor VIII, which activates factor X, which produces prothrombinase with factor V.

Question 10

What is haemostasis?

Answer 10

The maintenance of fluid blood flow, by a clot forming to stop the loss of blood but maintain blood flow through the vessel and prevent infarction.

Question 11

What is thrombosis?

Answer 11

Pathological manifestation of haemostasis, causing hypoxia and tissue damage.

Question 12

What is the final stage of haemostasis called, when the fibrin fibres pull the platelet plug into a more robust clot and the damaged ends of the vessel wall together?

Answer 12

Clot retraction.

Question 13

What is thrombocythaemia?

Answer 13

Too high platelet count.

Question 14

What is TTP and what causes it?

Answer 14

Thrombotic Thrombocytopenic Purpura. It is a rare side effect of clopidogrel (anti-thrombotic drug which inhibits platelet aggregation by blocking the pyrimidine receptor on platelets so the platelet agonist ADP can’t bind and activate them - also happens to inactivate the enzyme that breaks up von Willebrand Factor produced by endothelial cells, which instead forms large molecules that platelets bind to and form microemboli).

Question 15

Name the three stages of haemostasis.

Answer 15

Vascular spasm, primary haemostasis (platelet plug formation), secondary haemostasis (coagulation).

Question 16

What is contained in the alpha granules of platelets?

Answer 16

Adhesion proteins e.g von Willebrand Factor, platelet specific proteins, membrane proteing (glycoproteins).

Question 17

What is contained in the dense (darkly staining) granules of platelets?

Answer 17

Vasoconstrictive agents (e.g serotonin), platelet agonists (ADP, ATP, thromboxane), Ca2+ and Mg2+.

Question 18

What is the name of the receptors on the platelet membranes that bind to the platelet agonist ADP?

Answer 18

Pyrimidine receptors.

Question 19

Why do the binding of collagen and von Willebrand factor etc cause an immediate shape change in platelets?

Answer 19

The receptors these adhesion proteins bind to are directly connected to cytoskeletal proteins inside the platelet.

Question 20

What is the most important factor causing platelets to roll along the subendothelium and expose more of their glycoproteins to it for adhesion?

Answer 20

The sheer mechanical force of the blood flow.

Question 21

What is another name for clotting factors (inactive precursors of enzymes)?

Answer 21

Zymogens.

Question 22

What causes the extrinsic pathway of coagulation to be initiated?

Answer 22

Damage to cells outside of the blood vessel which causes them to release Tissue Factor, which activates and forms a complex with factor VII, which activates factor X and V to form prothrombinase.

Question 23

What happens in the common pathway of coagulation?

Answer 23

Prothrombinase converts prothrombin to thrombin. Thrombin then converts soluble fibrinogen to insoluble fibrin. In the presence of activated factor XIII, fibrin forms a cross-linked fibrin clot, and clot retraction occurs.

Question 24

Why is there a change in the light absorbed by the platelet rich plasma after it has been activated in platelet aggregometry?

Answer 24

At first the light absorbed increases as the platelets change shape and the mixture is more opaque, then the light absorbed decreases as the platelets form a plug and the light is able to travel through the colourless plasma.

Question 25

What is immune thrombocytopenia?

Answer 25

IgG coated platelets are cleared by macrophages in the spleen and Kupffer cells, so circulating platelets drop.

Question 26

What is the name of the rash of small haemorrhages the patient can get in a mild case of thrombocytopenia?

Answer 26

Petechia.

Question 27

Why does aspirin act as an anti-thrombotic drug?

Answer 27

It is a COX inhibitor so stops the platelet agonist thromboxane from being produced from phospholipids by the COX-1 enzyme in platelets. Thromboxane drives the shape change of activated platelets.

Question 28

Name the ADP receptor (pyrimidine receptor) antagonist that can be used as an anti thrombotic drug, but carries a rare risk of TTP.

Answer 28

Clopidogrel.

Question 29

Name the anticoagulant that inhibits vitamin K, so some clotting factors are not synthesised. Name the test used to find the correct dose.

Answer 29

Warfarin. An INR (international normalised ratio) is used after a PT has been performed.

Question 30

Name the two forms of heparin.

Answer 30

Unfractionated heparin (UFH), and low molecular weight heparin (LMWH).

Question 31

How does heparin work?

Answer 31

Heparin binds to antithrombin so that it binds irreversibly to factor X or thrombin and stops coagulation.
UFH causes antithrombin to bind irreversible to thrombin and factor X, LMWH causes antithrombin to bind irreversibly to only factor X.

Question 32

Why is bruising associated with cholestasis?

Answer 32

Vitamin K is produced by microorganisms in the large intestine, and is lipid soluble so is absorbed with lipids in the jejunum.